FGF2 Antiproliferative Stimulation Induces Proteomic Dynamic Changes and High Expression of FOSB and JUNB in K-Ras-Driven Mouse Tumor Cells.

作者: Francisca Nathalia de Luna Vitorino , Fabio Montoni , Jaqueline Neves Moreno , Bruno Ferreira de Souza , Mariana de Camargo Lopes

DOI: 10.1002/PMIC.201800203

关键词:

摘要: Fibroblast growth factor 2 (FGF2) is a well-known cell proliferation promoter; however, it can also induce cycle arrest. To gain insight into the molecular mechanisms of this antiproliferative effect, for first time, early systemic proteomic differences induced by in K-Ras-driven mouse tumor line using quantitative proteomics approach are investigated. More than 2900 proteins quantified, indicating that terms associated with metabolism, RNA processing, replication, and transcription enriched among differentially expressed upon FGF2 stimulation. Proteomic trend dynamics indicate that, mainly DNA replication carbohydrate an stimulus delays their abundance changes, whereas stimulation accelerates other metabolic programs. Transcription regulatory network analysis indicates master regulators stimulation, including two critical factors, FOSB JUNB. Their expression dynamics, both Y1 (a murine model adenocarcinoma cells) human lines (SK-N-MC UM-UC-3) susceptible to effects, Both protein levels depend on fibroblast receptor (FGFR) src signaling. JUNB knockdown do not rescue cells from arrest FGF2; delay, underlies one namely, S-phase progression delay.

参考文章(52)
Ulrich Hübscher, DNA replication fork proteins. Methods of Molecular Biology. ,vol. 521, pp. 19- 33 ,(2009) , 10.1007/978-1-60327-815-7_2
Alan C. Rapraeger, Scott Guimond, Alison Krufka, Bradley B. Olwin, [11] Regulation by heparan sulfate in fibroblast growth factor signaling Methods in Enzymology. ,vol. 245, pp. 219- 240 ,(1994) , 10.1016/0076-6879(94)45013-7
Anthony DeBlasio, Joachim Yahalom, Mark Rubin, Huisheng Wang, Robert Wieder, Eyal Fenig, John Mendelsohn, Basic Fibroblast Growth Factor Causes Growth Arrest in MCF-7 Human Breast Cancer Cells while Inducing both Mitogenic and Inhibitory G1 Events Cancer Research. ,vol. 57, pp. 1750- 1757 ,(1997)
Rémi Buisson, Jessica L Boisvert, Cyril H Benes, Lee Zou, None, Distinct but Concerted Roles of ATR, DNA-PK, and Chk1 in Countering Replication Stress during S Phase. Molecular Cell. ,vol. 59, pp. 1011- 1024 ,(2015) , 10.1016/J.MOLCEL.2015.07.029
Hongyan Zhao, Debbie L. Cunningham, Andrew J. Creese, John K. Heath, Helen J. Cooper, FAIMS and Phosphoproteomics of Fibroblast Growth Factor Signaling: Enhanced Identification of Multiply Phosphorylated Peptides Journal of Proteome Research. ,vol. 14, pp. 5077- 5087 ,(2015) , 10.1021/ACS.JPROTEOME.5B00713
Peter Reichard, Interactions Between Deoxyribonucleotide and DNA Synthesis Annual Review of Biochemistry. ,vol. 57, pp. 349- 374 ,(1988) , 10.1146/ANNUREV.BI.57.070188.002025
Jacqueline Salotti, Matheus H. Dias, Marianna M. Koga, Hugo A. Armelin, Fibroblast growth factor 2 causes G2/M cell cycle arrest in ras-driven tumor cells through a Src-dependent pathway. PLOS ONE. ,vol. 8, ,(2013) , 10.1371/JOURNAL.PONE.0072582